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Tuesday, October 7, 2014

Engineering Mosquitoes to Spread Health

This
is a great review of developing strategies to combat mosquito carried
disease. Some are very promising and I am looking to see at least
one of these protocols properly globalized. Sooner or later we must
also take the battle to the problem of malaria.

Tropical
disease are now attracting ample attention and we can hope to make
them all managible once and for all. Better is the fact that rising
global incomes and communication is reaching the majority with some
form of modern medical support. Every form of intervention reduces
the loss of life even if it is a mosquito net.

Forty
years ago, this was all hopeless. That is no longer true at all and
that is a blessing.

.

Engineering
Mosquitoes to Spread Health

The promise of
transforming flying vectors of dengue fever into preventive-medicine
tools

When I eloped to the
Caribbean island of Roatan, Honduras, in February 2002, I returned
with a new husband, a tan, and a tropical illness.

Dengue fever started
as a dull ache in my lower back, and escalated quickly until it felt
as if I'd been hit with a baseball bat. My stomach went queasy, and I
took to bed, thinking I'd caught the flu. I drifted off to
sleep, only to wake up a few hours later, drenched in sweat and
shivering under a mound of blankets, elbows burning, hips and knees
aching. I crawled to the bathroom, where I spent the rest of the
night alternately hugging the toilet and collapsing onto the
blessedly cold tile floor.

Morning brought a
migraine, searing joint pain, and aching muscles. My fever spiked to
103, and my mouth tasted like metal. I vomited every day for the next
week. Blood tests indicated an inflamed liver, which meant I could no
longer rely on codeine to dull the unrelenting pain. During those two
weeks of agony, I occasionally longed for death, but dengue never
truly threatened to deliver.

I was lucky. According
to the World Health Organization, of the estimated 50 to 100 million
people infected with dengue, also known as "breakbone"
fever, each year, about 500,000—mostly children—will require
hospitalization for severe dengue, or dengue hemorrhagic fever. Of
those, more than 10,000 will die.

In recent decades,
the disease has spread dramatically, from the nine countries
that experienced epidemics before 1970 to more than 100 today, on
every continent but Antarctica. It made its way to France and
Croatia in 2010, and caused an outbreak of 2000 cases on Portugal's
Madeira Islands in 2012. Florida, Texas, and Hawaii have reported
dozens of cases in the past few years, almost all imported by
travelers returning from the Caribbean or South America. But as
Walter Tabachnic, director of the Florida Medical Entomological
Laboratory in Vero Beach, recently told TIME magazine,
"Sooner or later, our mosquitoes will pick it up and
transmit it to us. That is the imminent threat."

"The target
really is the pathogen, and we can use the mosquitoes to get at the
pathogen."

Dengue fever is spread
primarily by the aedes aegypti mosquito, and also by aedes
albopictus, more commonly known as the asian tiger mosquito. Aedes
aegypti is the culprit in nearly every dengue fever epidemic,
while aedes albopictus gets credit for most outbreaks of
chikungunya, an illness that produces symptoms similar to dengue, but
is rarely deadly. Both mosquitoes are adept at transmitting these
vector-borne illnesses to humans, as well as yellow fever and
encephalitis. Both also thrive in urban environments, particularly
indoors. Their eggs can hatch in the smallest bodies of
water, including the pools of liquid that collect around shower and
sink drains. Only the females bite, but they do so during
the day, which means bed nets offer no protection. There is no
vaccine for dengue, and no cure. Epidemics overwhelm local hospitals
and crash local economies.

In most places where
dengue fever and chikungunya are endemic, pesticides are a vital
element of local strategies to prevent outbreaks, alongside public
education campaigns encouraging people to rid their yards and homes
of standing water. Local mosquito-control workers drive trucks down
city streets,filling the air with toxic chemicals.

Besides being an
environmental and human health hazard, fogging campaigns are not
particularly effective, explains Haydn Parry. Parry is the CEO of
Oxitec, a U.K.-based company associated with Oxford University that
believes it has developed an alternative to pesticides: genetically
modified (GM) mosquitoes. Oxitec’s mosquito carries a
lethal gene that it then passes along to its offspring.
The modified males are bred in a laboratory, then released into the
wild, where they mate with local females, who lay eggs that will die
before reaching adulthood.

"With
insecticides, you have to take the product to the insect, which means
you have to take your fog or spray into people's houses, and people
don't like that. If a fogger machine is coming down the street,
people close their windows and doors,” Parry says. “You know that
50 percent or more of the places mosquitoes are breeding are in
people's houses, and you just can't get at them. The beauty of our
little mosquito is that they don't have to ask permission to go on to
someone's property. They are biologically programmed to find the
females."

Oxitec's OK513A
mosquito has been released and monitored in the Cayman Islands,
Malaysia, Brazil and the Florida Keys, with promising results, Parry
says.

"In every
open-air trial we've done in urban environments—even cities filled
with buckets of standing water because there is no running water—the
results are the same. We recently crashed the local aedes
aegypti population in Mandacaru, Brazil by 96 percent in just six
months," he says.

There is no vaccine
for dengue, and no cure. Epidemics overwhelm local hospitals.

That success has been
tempered by criticism, mainly from anti-GMO activists concerned about
the unintended consequences of meddling with Mother Nature. GeneWatch
U.K. accuses Oxitec of skimping on risk assessments required by the
Cartagena Biosafety Protocol and of releasing genetically modified
mosquitoes on an unsuspecting public overseas without their informed
consent.

"As a U.K.
company, Oxitec has legal obligations here to produce risk
assessments before releasing any mosquitoes. We are concerned that
they haven't been following those requirements, which means people in
other countries are being used as guinea pigs," says Helen
Wallace, GeneWatch U.K.'s director.

Critics are also
concerned about a complex ecosystem response. "Reducing the
numbers of aedes aegypti could increase the population
of aedes albopictus, and we might not only get more of that
species, but we may find that they evolve to be a more effective
transmitter of disease," Wallace says.

Furthermore, the
disease itself could be affected by population-suppression
techniques. "A partial or temporary reduction in mosquito
numbers can make dengue worse, because when people are bitten
frequently, starting at a young age, they are more likely to develop
cross-immunity to different serotypes of the dengue virus," she
explains. "So, any method that reduces frequency of
biting can make dengue hemorrhagic fever worse." [
someone is really saying this? ]

Dr. Anthony James,
mosquito researcher and distinguished professor of microbiology and
molecular genetics at the University of California, Irvine, shares
Wallace's skepticism of population suppression techniques, but for
different reasons.

"In large urban
areas, we'll never knock down enough mosquitoes to eliminate dengue.
We've tried. It's not sustainable. If you control dengue with
population suppression, the mosquitoes will come back and you'll have
to start over. So we have to go after the disease, not just the
mosquitoes."

He separates
vector-borne illness prevention strategies into two distinct camps:
bite and no-bite.

No-bite strategies
focus on preventing mosquitoes from biting people, either by
suppressing the population with pesticides and "sterile"
mosquitoes, or by keeping mosquitoes away from people with window
screens, insect repellents, and protective clothing.

Bite strategies, on
the other hand, "recognize that it is the pathogen and not the
mosquito that is important here," James says. Before his funding
dried up, he was developing a strain of genetically engineered aedes
aegypti mosquitoes that still carried the dengue virus, but couldn't
transmit it to humans.

He explains that the
dengue virus starts in the mosquito's midgut and moves to its
salivary glands, allowing females to transfer the virus to the people
they bite. His team was able to insert a gene into the mosquitoes
that prevents the transfer to the salivary glands, resulting in "100
percent knockout of dengue 2," one of five serotypes of the
virus.

"The target
really is the pathogen, and we can use the mosquitoes to get at the
pathogen," James says.

That's the strategy
also being followed by Dr. Scott O'Neill, medical entomologist, dean
of the faculty of science at Monash University in Melbourne, and
leader of an international team of scientists working together on
theEliminate Dengue project. They have managed to infect
the aedes aegypti mosquito with a naturally-occurring bacteria
called Wolbachia that effectively vaccinates the mosquitoes
against the dengue virus. And rather than using their technology to
suppress the local mosquito population, they release legions of
vaccinated males and females to mate with, and eventually replace,
their counterparts in the wild.

"We're not using
any GM technology,” O’Neill says. “I'm a fan of what can be
done with GM, but there is resistance and concern in communities, so
that distinction is important. We have high acceptability with what
we're doing because Wolbachia is a naturally-occurring
bacterium."

In fact, Wolbachia is
already present in 60 percent of insects, including many species of
mosquitoes. This is one of the reasons Eliminate Dengue's research
projects in Australia, Indonesia, Vietnam, and Brazil have met
with very little opposition.

Another reason is
community outreach. "In Cairns [Australia] we went door-to-door
to get people’s individual consent,” O’Neill says. Mosquitoes
can only travel a few hundred feet from where they're hatched, and
“If they didn’t want it, we didn’t release at or next to their
homes. We spent years doing community engagement, and taking all
concerns seriously. We undertook additional studies to respect the
views of the community and ensure they were being heard and listened
to. That is the same approach we have taken everywhere else. We've
got 95 percent support in Australia, and the same in Vietnam."

Evidence from field
trials suggests that the population-replacement strategy is working.
In 2011, the team released vaccinated mosquitoes for 10 weeks in two
Cairns communities. A few months after the release, all the
mosquitoes in those communities had Wolbachia, and three years
later, they still do, according to O'Neill. But the jury is still out
on whether this method—or Oxitec's,—can actually prevent dengue
outbreaks.

"Globalization is
coming, whether we like it or not. We need to address this now,
because we don't make good decisions in crisis mode."

"In order to
measure a change in dengue transmission, we'll need large
deployments, to cities of perhaps half a million people,"
O’Neill says.

Oxitec's Parry
concurs. "There is no evidence yet that we have cut down
instances of dengue, but that is the same for insecticides,” he
says. “If you wanted to run a clinical trial to prove the link
between this and the disease, you'd need a scale of at least 250,000
people, and that's a bigger trial than we can currently accomplish."

While GeneWatch U.K.
points to this lack of evidence as another reason to drop GM mosquito
projects in favor of developing a viable vaccine for humans,
UC-Irvine's James sees it differently.

"I encourage all
of it. It would be a real shame if we shut down any promising
research. In the fight against malaria, we focused on DDT and
chloroquine and shut off all other research. Then resistance [to
chloroquine] kicked in, and we didn't have a viable alternative to
replace it with," he says.

James also says he
thinks government and public-health officials in the U.S. should
increase funding immediately, before dengue fever and chikungunya
establish themselves as a serious threat here. "Globalization is
coming, whether we like it or not. That means we have to go to the
places where the disease is already rampant. We need to address this
now, because we don't make good decisions when we're in crisis mode."

In the meantime, even
the world's top mosquito researchers must rely on low-tech methods to
protect themselves from vector-borne illness when they’re in the
field. "For all the science in the world, your best protection
is a long sleeve shirt,” Parry says.

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Apr 2017 - 4.1 Mil Pg Views, March 2013 - Posted my paper introducing CLOUD COSMOLOGY & NEUTRAL NEUTRINO rigorously described as the SPACE TIME PENDULUM, September 2010 I am pleased to report that my essay titled A NEW METRIC WITH APPLICATIONS TO PHYSICS AND SOLVING CERTAIN HIGHER ORDERED DIFFERENTIAL EQUATIONS' has been published in Physics Essays(AIP) and appeared in their June 2010 quarterly. 40 years ago I took an honors degree in applied mathematics from the University of Waterloo. My interest was Relativity and my last year there saw me complete a 900 level course under Hanno Rund on his work in relativity,as well as differential geometry(pure math) and of course analysis. I continued researching new ideas and knowledge since that time and I have prepared a book for publication titled Paradigms Shift&. I maintain my blog as a day book and research tool to retain data and record impressions and interpretations on material read. Do join my blog and receive Four items of interest daily Monday through Saturday.